Latest research in nootropic therapy of patients with chronic cerebral circulation insufficiency.

OBJECTIVE: Aim: To analyze latest research on the usage of choline alfoscerate and ethylmethylhydroxypyridine succinate (EMHPS) as nootropic therapy for patients with chronic cerebral circulation insufficiency (CCCI). PATIENTS AND METHODS: Materials and Methods: Bibliosemantic, comparative and system analysis methods were used in the study. The proposed recommendations are developed on the basis of the analysis of modern literature, the results of randomized studies and meta-analyses, authoritative studies devoted to the study of the CCCI problem. CONCLUSION: Conclusions: The combination of EMHPS with choline alfoscerate for the complex treatment of CCCI and associated syndromes improves the functions of the endothelium, leads to asthenic syndrome, indicators of stress, depression and anxiety decreasing has a positive effect on the cognitive impairment and complications' progress reduction.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

A meta-analysis of the effectiveness of Yangxue Qingnao granules for the treatment of chronic cerebral circulation insufficiency.

OBJECTIVE: Yangxue Qingnao granules (YXQNG), which translates to granules that tonify the blood and clear liver heat, are widely available in China for the treatment of Chronic Cerebral Circulation Insufficiency (CCCI). This systematic review aimed to evaluate the effectiveness and safety of YXQNG in treating CCCI. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase, the Chinese National Knowledge Infrastructure, and the Wanfang Database were searched from their inception to February 2019. Randomized controlled trials of YXQNG used alone or in combination with other drugs against a placebo, with no intervention or used with other drugs in CCCI patients were identified. The reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. The Cochrane risk of bias assessment tool was used for quality assessment. RESULTS: A total of 31 RCTs and 2,877 patients were selected. The meta-analysis indicated that the ratio between the combined RR of the total effective rate and the 95% confidential interval (95% CI) was 1.21 (1.17, 1.26). The combined MD of transcranial Doppler (TCD) detecting carotid artery, vertebral artery, and basilar artery blood flows (95% CI), respectively, were 8.84 (5.83, 11.85), 4.72 (3.71, 5.73), and 3.89 (3.03, 4.76). The combined MD of plasma viscosity and fibrinogen, respectively, were -0.35 (-0.40, -0.30) and -0.81 (-1.12, -0.50). Serious adverse effects were not reported in all the included trials. CONCLUSION: This systematic review revealed that YXQNG could increase cerebral blood flow in patients with CCCI and improve their symptoms, with no serious adverse effects. Since the literature reviewed was affected by factors such as lower quality of the included studies, the systematic evaluation's conclusion is not very reliable. Thus, more rigorously designed trials are needed.

Potential Applications of Remote Limb Ischemic Conditioning for Chronic Cerebral Circulation Insufficiency.

Chronic cerebral circulation insufficiency (CCCI) refers to a chronic decrease in cerebral blood perfusion, which may lead to cognitive impairment, psychiatric disorders such as depression, and acute ischemic stroke. Remote limb ischemic conditioning (RLIC), in which the limbs are subjected to a series of transient ischemic attacks, can activate multiple endogenous protective mechanisms to attenuate fatal ischemic injury to distant organs due to acute ischemia, such as ischemic stroke. Recent studies have also reported that RLIC can alleviate dysfunction in distant organs caused by chronic, non-fatal reductions in blood supply (e.g., CCCI). Indeed, research has indicated that RLIC may exert neuroprotective effects against CCCI through a variety of potential mechanisms, including attenuated glutamate excitotoxicity, improved endothelial function, increased cerebral blood flow, regulation of autophagy and immune responses, suppression of apoptosis, the production of protective humoral factors, and attenuated accumulation of amyloid-ß. Verification of these findings is necessary to improve prognosis and reduce the incidence of acute ischemic stroke/cognitive impairment in patients with CCCI.

Normobaric oxygen: a novel approach for treating chronic cerebral circulation insufficiency.

Chronic cerebral circulation insufficiency (CCCI) is viewed as an alarming state induced by long-term reduction in cerebral perfusion, which is associated with neurological deficits and high risk of stroke occurrence or recurrence. CCCI accounts for a large proportion of both outpatients and inpatients with cerebrovascular diseases, while management of CCCI remains a formidable challenge to clinicians. Normobaric oxygen (NBO) is an adjuvant hyperoxygenation intervention supplied with one atmosphere pressure (1 ATA =101.325 kPa). A plethora of studies have demonstrated the efficacy of NBO on the penumbra in acute stroke. NBO has been shown to increase the oxygen pressure, raise the intracranial blood flow, protect blood-brain barrier and enhance neuroprotective effects. As similar underlying mechanisms are shared by the penumbra in stroke and the ischemic-hypoxic brain tissues in CCCI, we speculate that NBO may serve as a promising therapeutic strategy for attenuating short-term symptoms or improving long-term clinical outcomes among patients with CCCI. Due to the scant research exploring the efficacy and safety of NBO for treating CCCI so far, both experimental and clinical studies are warranted to verify our hypothesis in the future.

Effect of Modified Bazhentang on Cerebrovascular Reserve and Hemorheology in Patients with Chronic Cerebral Circulation Insufficiency / 中国实验方剂学杂志

Objective: To observe the effect of modified Bazhentang on cerebrovascular reserve and hemorheology in patients with chronic cerebral circulation insufficiency. Method: Totally 80 patients treated at Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from January 2018 to June 2018 in line with the inclusion criteria were randomly divided into the observation group (40 cases) and the control group (40 cases) using the random sequence of Stata 13.0. Both groups received basic treatments, such as antihypertensive, hypoglycemic and lipid-lowering. In addition to the therapy of the control group, the control group was also given nimodipine tablet treatment, and the observation group was given modified Bazhentang treatment, with a total course of 30 days. Before and after treatment, transcranial doppler ultrasonography (TCD) was used to detect the cerebrovascular reserve function of the two groups, so as to evaluate the clinical efficacy, and detect the hemorheology, blood routine, hepatic and renal function. Result: The effective rate of the observation group was 92.5%, and that of the control group was 80%. The clinical efficacy of the observation group was better than that of the control group (PPPPPConclusion: Modified Bazhentang can effectively treat chronic cerebral circulation insufficiency. By improving the function of cerebrovascular reserve and cerebral blood flow, it can alleviate clinical symptoms without safety problems, so as to provide a theoretical basis for the treatment of chronic cerebral circulation insufficiency with traditional Chinese medicine.

Advances in chronic cerebral circulation insufficiency.

Chronic cerebral circulation insufficiency (CCCI) may not be an independent disease; rather, it is a pervasive state of long-term cerebral blood flow insufficiency caused by a variety of etiologies, and considered to be associated with either occurrence or recurrence of ischemic stroke, vascular cognitive impairment, and development of vascular dementia, resulting in disability and mortality worldwide. This review summarizes the features and recent progress of CCCI, mainly focusing on epidemiology, experimental research, pathophysiology, etiology, clinical manifestations, imaging presentation, diagnosis, and potential therapeutic regimens. Some research directions are briefly discussed as well.

[Analysis of CT perfusion imaging in chronic cerebral circulatory insufficiency and its relationship with crossed cerebellar diaschisis].

Objective: To investigate the change of cerebral microcirculation of chronic cerebral circulation insufficiency(CCCI) patients and the relationship between CCCI and crossed cerebellar diaschisis(CCD)by using 320-detector row of low-dose volume CT perfusion imaging. Methods: A total of 158 patients (103 males, 55 females, from 45 to 82 years old, the mean age was 62.9) with symptoms of CCCI were admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2013 to January 2016. Low-dose CTP imaging of whole brain was performed to them using 320-detector row volume CT scanner. The perfusion parameters such as cerebral blood flow(CBF), cerebral blood volume(CBV), mean transit time(MTT), time to peak(TTP) and DLY in both cerebral blood supply areas and cerebellum were got, so were the 4-dimensional CTA images, and rCBF, rCBV, rMTT and rTTP were calculated by ipsilateral/contralateral value. Comparative t-test and independent t-test were applied to analyzing these parameters quantitatively.Chi-square test and Logistic regression model were applied to analyzing the related clinical risk factors. Results: (1) All 108 patients in CCCI group showed asymmetric perfusion within two cerebral hemispheres in CTP images. The CBF, CBV of diseased side were lower than the contralateral mirror area (t(CBF)=-12.89, t(CBV)=-7.031, P(CBF, CBV)<0.001); the MTT of the diseased side was shorter than the contralateral mirror area (t(MTT) =13.310, P(MTT)<0.001); the TTP of the diseased side was longer than the contralateral mirror area (t(TTP)=-4.012, P(TTP)<0.001). The rCBF and rCBV of CCCI group were lower than that in non-CCCI group (t(rCBF)=3.079, t(rCBV)=2.760, P(rCBF, rCBV)<0.01), while the rTTP of CCCI group was longer than that in non-CCCI group (t(rTTP)=4.846, P(rTTP)<0.001). (2)The results of Chi-square test showed that the differences of gender (χ(2)=4.036, P=0.045), hyperlipidemia (χ(2)=7.687, P=0.006), as well as smoking (χ(2)=11.868, P=0.001) had statistical significance between CCCI group and non-CCCI group.Multi-factor Logistic regression analysis showed that hyperlipidemia (OR value=3.736, P=0.016) and smoking (OR value=4.641, P=0.01) were the risk factors of CCCI, while gender had no relationship with it.(3)The incidence of CCD was 18.5% in the CCCI group, and at the same time, the supratentorial corresponding blood supply areas were classified.A total of 10(34.5%) cases were in blood supply area of posterior cerebral artery, 6(20.7%) cases were in blood supply area of middle cerebral artery, 12(41.4%) cases were of anterior cerebral artery, while only 1(3.5%) case was of basal ganglia, in which 4 cases were in blood supply area of posterior cerebral artery, another 4 cases were middle cerebral artery, 7 cases were of anterior cerebral artery and no case of basal ganglia respectively leading CCD alone. Conclusions: CTP could display the microcirculation situation of abnormal brain tissue perfusion area intuitively and quantitatively. Additionally, it could reflect the degree of relationship between cerebral several blood supply areas and cerebellum.

Clinical Study on Bushen Huoxue Decoction for Elderly Patients with Chronic Cerebral Circulation Insufficiency / 中国中医药信息杂志

Objective To observe the effects of Bushen Huoxue Decoction on clinical symptom, vertigo degree and cognitive function for elderly patients with chronic cerebral circulation insufficiency (CCCI); To explore its possible mechanism. Methods Totally 70 cases were randomly divided into observation group and control group according to the random digits table method, with 35 cases in each group. The two groups were given Western medicine consisting of blood pressure control, glucose control and blood lipid control. Based on this, the control group was given Flunarizine Hydrochloride capsules, 5 mg once a day orally before sleeping. The observation group was given Bushen Huoxue Decoction, one dose a day and taken twice a day. The treatment lasted for 30 days. The TCM symptom score, Chinese version of dizziness handicap inventory (DHI) and Montreal cognitive assessment (MoCA) score were observed. The mean blood flow velocity (Vm) of basilar artery (BA), bilateral vertebral artery (VA), bilateral middle cerebral artery (MCA) and the content of plasma acid phospholipid (AP) were detected, and the clinical efficacy was evaluated. Results The total effective rate of the observation group was 94.3％ (33/35), which was significantly higher than that of 82.9％ (29/35) in the control group, with statistical significance (P<0.05); after treatment, the TCM symptom score, DHI score, and the content of plasma AP were significantly lower than those of pre-treatment in the same group (P<0.05); the MoCA score and the Vm of VA, LBA, RBA, LMCA, RMCV were significantly higher than those of pre-treatment in the same group (P<0.05); the TCM symptom score, DHI score, MoCA score, the Vm of LVA, LMCA, RMCA and the content of plasma AP in the observation group were improved better than those in the control group, with statistical significance (P<0.05). Conclusion Bushen Huoxue Decoction has an obvious therapeutic effects for elderly patients with CCCI, which can improve clinical symptom, vertigo degree and cognitive level, which possible mechanism is related to increasing the cerebral blood flow velocity and reducing the content of plasma AP.

Montreal cognitive assessment and analysis of related factors for cognitive impairment in patients with chronic cerebral circulation insufficiency.

BACKGROUND: Chronic cerebral circulation insufficiency (CCCI) refers to cerebral dysfunctions that lead to cerebral vascular pathological changes. Our aim is to identify factors related to cognitive impairment in CCCI. METHODS: CCCI patients (n=102) were assessed with the Montreal cognitive assessment (MoCA) to analyze cognitive impairment. Patients were divided into two groups according to MoCA scores: (1) cognitive dysfunction and (2) normal cognitive function. We compared the clinical information with univariate and multivariate logistic regression analyses and identified major risk factors related to cognitive impairment in CCCI. RESULTS: Age (p=0.007, OR=3.768, χ2=7.173), leukoaraiosis (p=0.002, OR=6.231, χ2=9.478), a history of hypertension (p=0.021, OR=3.078, χ2=5.307), a history of hyperlipidemia (p=0.016, OR=3.429, χ2=5.795), and the number of vascular risk factors (p=0.019, χ2=9.921) were related to cognitive impairment by univariate analysis. Age (p=0.070, OR=2.689, 95% CI=0.923±7.837) and leukoaraiosis (p=0.012, OR=4.531, 95% CI=1.401±14.667) were significant by multivariate logistic regression analysis. Age (r=-0.585, p<0.01) had a marked negative correlation with MoCA scores. There were significant differences in the MoCA subscale scores, including visuospatial and executive capacity (p<0.01), attention and calculation (p<0.01), and delayed recall (p<0.01), in patients with different degrees of leukoaraiosis. Patients with CCCI had a higher incidence of cognitive impairment (78.4%). CONCLUSIONS: Changes in visuospatial and executive capacity, delayed recall, and language function represent cognitive manifestations in CCCI. Age and leukoaraiosis have the strongest effects on cognitive impairment morbidity and can aggravate cognitive impairment.

Clinical analysis of nicergoline in treatment for 80 patients with chronic cerebral circulation insufficiency / 局解手术学杂志

Objective To observe the curative effect of nicergoline in the treatment of chronic cerebral circulation insufficiency ( CC-CI) . Methods 160 cases with CCCI were randomly divided into the treatment group which were administered 10 mg of oral Nicergoline, three times per day for one month,and the control group which were given 20 mg of oral nimodipine,three times per day for one month. The clinical effective rate and the transcranial Doppler ultrasound ( TCD) between the two groups before and after treatment were observed. Results There were significant difference in clinical effective rate and TCD index assessment between the two groups(P<0. 05). Conclu-sion Nicergoline is an effective and safe treatment for chronic cerebral circulation insufficiency.

Advance in Chronic Cerebral Circulation Insufficiency (review) / 中国康复理论与实践

@# Chronic cerebral circulation insufficiency (CCCI) was preferred as a new disease name in recent years. It can cause ischemic and different degrees patho-damage in brain tissue. Accordingly, it lead to decrease the function in perception and cause aphronesia. It had attracted great attention for native and foreign researchers. In this article, the authors will summarize recent research province on empirical research, clinic auxiliary diagnosis and treatment status in the CCCI.

Effects of Hyperbaric Oxygen Combined with Fastigial Nucleus Stimulation on Chronic Cerebral Circulation Insufficiency with Transcranial Doppler and Electroencephalography / 中国康复理论与实践

@#Objective To observe the of changes of cerebral blood flow and electroencephalography in chronic cerebral circulation insufficiency (CCCI) treated with fastigial nucleus stimulation (FNS) and hyperbaric oxygen (HBO). Methods 144 cases of CCCI were divided into 4 groups: 36 cases were treated with FNS and HBO, 36 cases with FNS, 36 cases with HBO, 36 cases without any treatment as control group. The blood velocity of anterior, middle, posterior cerebral arteries, vertebral artery and basilar artery were measured with transcranial Doppler (TCD) and the brain waves （α, β, δ, θ） were recorded with electroencephalography (EEG) before and after the treatment. Results Compared with the control, the brain blood velocity and α wave increased in all the treatment groups, especially in the HBO+FNS group, while β, δ, θ waves decreased (P<0.05). Conclusion FNS and HBO can increase cerebral blood flow and improve the cerebral function respectively.